Ph.D. / Epilepsy is a multidimensional disorder that extends beyond the medical implications to impact nearly every aspect of the person's life, as well as the lives of the people in the surrounding environment. Intractable epilepsy has a poor prognosis with possible worsening of seizures and cognitive decline over time. Anterior temporal lobe surgery for epilepsy provides an opportunity for the alleviation of seizures; however there are potential risks, to memory in particular. Research on surgery outcome thus far has evaluated outcome from a linear paradigm and has studied impact of surgery on isolated areas of function, the results derived from this have been largely inconsistent. So far, there has been very little research that focuses on the person as a whole, and as yet there has been no integrated approach to studying surgical outcome. The aim of the current study was therefore to investigate the impact of anterior temporal lobe surgery, specifically the symptomatic and functional surgical outcomes, in an integrated and holistic manner. This was done in accordance with the paradigm of complex systems theory as a critique of the previous literature in this field, and to gain a more holistic understanding of surgical outcome. A combination of methodologies was employed in order to achieve this. The sample consisted of male (n=10) and female (n=24) patients with intractable epilepsy undergoing left-sided (n=13) and right-sided (n=21) temporal lobe surgery at the Milpark Hospital Johannesburg between the ages of 14 and 58 (mean = 39 years), over a period of seven years. A pretest-posttest design was employed to obtain quantitative data (n=34). Post surgical assessments were conducted up to seven years post surgery (mean=3.6 years). Pre and post surgery assessment included neurocognitive functioning, particularly memory and language functions, by means of the Rey Complex Figure Test, Wechsler Memory Scale-Ill, and Controlled Oral Word Association Test; as well as emotional functioning, particularly depression and anxiety, by means of the Beck Depression lnventory-11 and Beck Anxiety lnventory-11. The quantitative data was subjected to statistical analysis of the sample as a whole, as well as gender and side of surgery comparisons, and included tests of normality of distribution of the data; the paired samples t-test; the independent samples t-test; the Wilcoxon Signed Ranks test; the Mann-Whitney U test; and the Wilks' Lambda test. A semi-structured interview was also conducted (n=30) in order to obtain qualitative data on the functional (psychosocial) aspects of outcome. The interview included an assessment of postoperative seizure outcome; changes in daily activity functions; the client's report on positive and negative outcomes of surgery; quality of life changes and satisfaction with surgery. The qualitative data was analysed using the methods of open coding and axial coding. The results for neuropsychological function reflected known lateralization effects with memory showing auditory-verbal memory deficits after left-sided surgery; and visual (figural) memory deficits after right-sided surgery. Gender differences reflected known neuropsychological differences with female superiority in verbal fluency and a male advantage on visual-spatial tasks. Importantly, there was no relationship between neuropsychological deficit and decrements in daily activity functions, emotional functioning or quality of life. This indicates little impact of neuropsychological deficit post surgery and may be an indication of the effectiveness of the preoperative screening procedures. The results for emotional functioning showed a statistically significant improvement in the 'moderate/severe' depression and anxiety groups from pre to post surgery. This indicates a substantial improvement in both depression and anxiety for this severity group. The qualitative results showed that surgery rendered 74% of the sample seizure free, 15% showing worthwhile improvement, and 11% no change or worse seizures. Seizure outcome however did not determine quality of life changes, even those with some improvement or no change still reported an improvement in quality of life post surgically. The functional outcomes showed little postoperative change in daily activity functions (driving, occupational functioning and marital status) but still a reported improvement in quality of life. There were far more reports on perceived positive than negative outcomes. The most positive benefit of surgery, as reported by participants, was that of increased feelings of control, decreased helplessness, and less anxiety and worry of having seizures. The overwhelming majority of participants reported improved quality of life (90%) and satisfaction with surgery (93%).

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19272号 / 医博第4036号 / 新制||医||1011(附属図書館) / 32274 / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 村井 俊哉, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Memory impairments are common in individuals with temporal lobe epilepsy (TLE). This is understandable given that temporal lobe brain structures involved in TLE play a central role in encoding memories. It is widely accepted that individuals whose seizure focus is in the left temporal lobe (LTLE) tend to have verbal memory impairments, whereas individuals whose seizure focus is in the right temporal lobe (RTLE) tend to have visuospatial memory impairments. However, evidence of functional subdivisions within the left and right temporal lobes in both the animal and human literature suggest that more specific subtypes of memory impairment may exist in TLE based on differences in seizure foci. The aim of this study was to identify more specific subtypes of memory-impairments in patients with intractable TLE using several measures of memory functioning and cluster analysis. Identification of more specific memory subtypes in TLE could have prognostic significance for patients and contribute to our knowledge about the organization of memory systems of the human brain. Four memory subtypes were identified in this sample: 1) patients with mild to moderate figural memory deficits; 2) patients with moderate to severe figural memory deficits, mild facial recognition deficits, and mild attention/concentration deficits; 3) patients with severe figural memory deficits and mild verbal episodic memory deficits; and 4) patients with no episodic or semantic memory deficits. Unexpectedly, the subtypes found did not exhibit the expected pattern of verbal memory impairments with left temporal lobe damage/dysfunction or visuospatial memory impairments with right temporal lobe damage/dysfunction. However, consistent with the literature, there was a trend towards some clusters with better verbal memory having higher left hippocampal volumes; and a trend towards one cluster with facial recognition deficits having lower anterior temporal lobe volumes. Small sample sizes in this study limited the ability to clearly validate many of the cluster differences, particularly differences in brain volumes. Nevertheless, the results of this study support the hypothesis that subtypes of memory impairment do exist in patients with TLE. With larger sample sizes, it is plausible that additional subtypes may be found, or the characteristics of the subtypes found may become clearer.

No description available.

La recherche dans le domaine de la mémoire sémantique a permis de documenter l’effet de concrétude (avantage pour les mots concrets relativement aux mots abstraits), et plus récemment, l’effet de concrétude inverse (avantage pour les mots abstraits relativement aux mots concrets). Ces effets, observés chez le sujet sain et dans différentes populations cliniques en neurologie, ont suscité de nombreuses interprétations théoriques, autant sur le plan cognitif que neuroanatomique. En effet, cette double dissociation entre les deux types de concepts suggère que leur traitement doit reposer au moins en partie sur des processus mentaux et neuroanatomiques distincts. Néanmoins, les origines de ces différences restent largement débattues et sont caractérisées par une absence notable de consensus. L’objectif principal de la présente thèse est d’explorer les substrats cérébraux sous-tendant la compréhension des concepts concrets et abstraits. Dans un premier temps, un article de revue de la littérature dresse un état des lieux des connaissances actuelles portant sur le traitement sémantique des mots concrets et abstraits ainsi que sur leurs fondements cérébraux. Cet article met une emphase particulière sur les différences inter-hémisphériques dans le traitement des mots concrets et abstraits (Article 1). Dans un deuxième temps, une étude expérimentale de la compréhension des mots concrets et abstraits a été réalisée auprès de populations cliniques rares, des patients ayant subi soit i) une résection unilatérale de la partie antérieure du lobe temporal (temporo-polaire), soit ii) une résection unilatérale de la région hippocampique (temporale interne) (Article 2). Le premier article fait ressortir la grande hétérogénéité des résultats dans le domaine, et suggère que les différences observées dans le traitement des mots concrets et abstraits peuvent difficilement être interprétées seulement en termes de différences inter-hémisphériques. Les résultats du second article indiquent qu’une lésion de la région temporale antérieure gauche ou droite entraîne une atteinte plus marquée des concepts concrets comparativement aux abstraits, alors qu’une lésion unilatérale des régions temporales internes affecte de manière équivalente le traitement sémantique des deux types de concepts. Les implications théoriques et cliniques de ces résultats sont discutées, ainsi que les limites et perspectives futures. / Research in the field of semantic memory has allowed to document the concreteness effect (advantage for concrete words relative to abstract words), and more recently, the reversal of the concreteness effect (advantage for abstract words relative to concrete words). These effects, observed in healthy subjects and in different clinical neurological populations, have yielded numerous theoretical interpretations, both on cognitive and on neuroanatomical levels. Indeed, this double dissociation between the two kinds of concepts suggests that their processing relies at least partly on distinct mental and neuroanatomical bases. Nevertheless, the origins of those differences remain largely debated and are marked by a notable lack of consensus. The principal goal of the present thesis is to explore the cerebral substrates underlying the comprehension of concrete and abstract concepts. First, a literature review summarizes current knowledge about the processing of concrete and abstract concepts as well as their neural bases. This article emphasizes in particular the inter-hemispheric differences in the processing of those concepts (Article 1). Secondly, an experimental study of the comprehension of concrete and abstract concepts was conducted with a rare clinical population, patients who have undergone either i) a unilateral resection of the anterior part of the temporal lobe (temporal pole), either ii) a unilateral resection of the hippocampal region (internal temporal structures) (Article 2). The first article highlights the important heterogeneity of the results in the field, and suggests that the observed differences in the processing of concrete and abstract concepts can hardly be explained solely in terms of inter-hemispheric differences. Results of the second article indicate that damage to anterior temporal regions, either left or right, can cause a more pronounced deficit of concrete concepts, as compared to abstract concepts, while damage to internal temporal regions affects the semantic processing of both kinds of concepts in an equivalent way. The theoretical and clinical implications of these results are discussed, and the limits and future research perspectives are also addressed.

La recherche dans le domaine de la mémoire sémantique a permis de documenter l’effet de concrétude (avantage pour les mots concrets relativement aux mots abstraits), et plus récemment, l’effet de concrétude inverse (avantage pour les mots abstraits relativement aux mots concrets). Ces effets, observés chez le sujet sain et dans différentes populations cliniques en neurologie, ont suscité de nombreuses interprétations théoriques, autant sur le plan cognitif que neuroanatomique. En effet, cette double dissociation entre les deux types de concepts suggère que leur traitement doit reposer au moins en partie sur des processus mentaux et neuroanatomiques distincts. Néanmoins, les origines de ces différences restent largement débattues et sont caractérisées par une absence notable de consensus. L’objectif principal de la présente thèse est d’explorer les substrats cérébraux sous-tendant la compréhension des concepts concrets et abstraits. Dans un premier temps, un article de revue de la littérature dresse un état des lieux des connaissances actuelles portant sur le traitement sémantique des mots concrets et abstraits ainsi que sur leurs fondements cérébraux. Cet article met une emphase particulière sur les différences inter-hémisphériques dans le traitement des mots concrets et abstraits (Article 1). Dans un deuxième temps, une étude expérimentale de la compréhension des mots concrets et abstraits a été réalisée auprès de populations cliniques rares, des patients ayant subi soit i) une résection unilatérale de la partie antérieure du lobe temporal (temporo-polaire), soit ii) une résection unilatérale de la région hippocampique (temporale interne) (Article 2). Le premier article fait ressortir la grande hétérogénéité des résultats dans le domaine, et suggère que les différences observées dans le traitement des mots concrets et abstraits peuvent difficilement être interprétées seulement en termes de différences inter-hémisphériques. Les résultats du second article indiquent qu’une lésion de la région temporale antérieure gauche ou droite entraîne une atteinte plus marquée des concepts concrets comparativement aux abstraits, alors qu’une lésion unilatérale des régions temporales internes affecte de manière équivalente le traitement sémantique des deux types de concepts. Les implications théoriques et cliniques de ces résultats sont discutées, ainsi que les limites et perspectives futures. / Research in the field of semantic memory has allowed to document the concreteness effect (advantage for concrete words relative to abstract words), and more recently, the reversal of the concreteness effect (advantage for abstract words relative to concrete words). These effects, observed in healthy subjects and in different clinical neurological populations, have yielded numerous theoretical interpretations, both on cognitive and on neuroanatomical levels. Indeed, this double dissociation between the two kinds of concepts suggests that their processing relies at least partly on distinct mental and neuroanatomical bases. Nevertheless, the origins of those differences remain largely debated and are marked by a notable lack of consensus. The principal goal of the present thesis is to explore the cerebral substrates underlying the comprehension of concrete and abstract concepts. First, a literature review summarizes current knowledge about the processing of concrete and abstract concepts as well as their neural bases. This article emphasizes in particular the inter-hemispheric differences in the processing of those concepts (Article 1). Secondly, an experimental study of the comprehension of concrete and abstract concepts was conducted with a rare clinical population, patients who have undergone either i) a unilateral resection of the anterior part of the temporal lobe (temporal pole), either ii) a unilateral resection of the hippocampal region (internal temporal structures) (Article 2). The first article highlights the important heterogeneity of the results in the field, and suggests that the observed differences in the processing of concrete and abstract concepts can hardly be explained solely in terms of inter-hemispheric differences. Results of the second article indicate that damage to anterior temporal regions, either left or right, can cause a more pronounced deficit of concrete concepts, as compared to abstract concepts, while damage to internal temporal regions affects the semantic processing of both kinds of concepts in an equivalent way. The theoretical and clinical implications of these results are discussed, and the limits and future research perspectives are also addressed.